There is an enormous need for the development of a new class of chemical microsensors that are versatile, selective, sensitive and reliable to allow investigation of the neurobiological mechanisms of behavior and disease symptoms. Currently, the preferred method for monitoring neurotransmitters in vivo real time is fast- scan cyclic voltammetry (FSCV) and the preferred microelectrode material is carbon fiber. We propose here the next generation electrode material, boron-doped ultrananocrystalline diamond (BD UNCD) that offers superior sensitivity and specificity, fast response time, low background currents, long-term stability and resistance to fouling compared to carbon fibers. The goal is to develop a chronically implantable UNCD microsensor for long-term (i.e., months to years) neurochemical recording, especially if human compatible. The specific aims of this project are, (i) to develop a reliable UNCD film deposition process on a tantalum (Ta) wire substrate that is scalable and mass-producible, (ii) to demonstrate microelectrode electrochemical behavior (i.e. higher signal-to-noise ratio) of a patterned UNCD-Ta microsensor using cyclic voltammetry and potassium ferrocyanide solution and (iii) to demonstrate the unique advantages of UNCD microelectrodes by measuring dopamine with flow injection analysis and in the anesthetized rat brain. Some of the planned improvements include modifications to the Ta surface preparation process to increase film adhesion and selective patterning of insulators to produce "windows" of BD UNCD that should allow consistent microelectrode behavior. As a proof-of-concept, the electrodes will be used to measure dopamine (the most widely studied neurotransmitter) down to 10 nM physiological concentration. The proposed sensor could potentially be used for simultaneous measurement of dopamine and many other important neurotransmitters. If this project is successful, it will readily accomplish many NIH mission goals for the Division of Neuroscience and Basic Behavioral Science, specifically: 1) for "in vivo voltammetry" - the UNCD is bioinert and highly selective due to its surface chemistry and small pseudo capacitance;2) for "biocompatible biomaterials" - UNCD/parylene passivation is novel and completely biocompatible for chronic neurochemical sensing;3) for "nanotechnologies'" - application of UCND and nanometer thick insulators greatly advance the way in which probes are fabricated;and 4) for "biosensors"- UNCD can be easily modified with antibodies and oligonucleotide probes through photochemical or electrochemical means. A recent report suggests that the medical sensing market will reach $10.9 billion in 2012. If only 0.1% ($10.9 million) of that market is accessible by UNCD microelectrode technology, it would still be sufficient justification for the proposed work. Also, a greater understanding of real-time sensing of neurotransmitters from this project would enable alternative applications for the technology, including: low-cost, point-of-use, portable, implantable sensors for toxins, metabolites and disease biomarkers. PUBLIC HEALTH RELEVANCE: This project will develop a microsensor technology using Ultrananocrystalline diamond electrodes to further advance the neuroscience field (brain function and disease symptoms). Its versatility, sensitivity and reliability are ideally suited for real-time, chronic measurement of multiple neurochemicals and brain activity mapping.